Institution
Newcastle University
Education•Newcastle upon Tyne, United Kingdom•
About: Newcastle University is a education organization based out in Newcastle upon Tyne, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 31772 authors who have published 71187 publications receiving 2539147 citations. The organization is also known as: University of Newcastle upon Tyne.
Papers published on a yearly basis
Papers
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TL;DR: New longitudinal data derived from a histological analysis of tooth enamel suggest fewer differences between samples and smaller ranges of variation than in many radiographic studies and present a more realistic picture of worldwide variation in enamel formation times.
415 citations
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TL;DR: The first population-based clinical and molecular genetic study of Leber hereditary optic neuropathy in a population of 2,173,800 individuals in the North East of England indicates that LHON is not rare but has a population prevalence similar to autosomally inherited neurological disorders.
Abstract: We performed the first population-based clinical and molecular genetic study of Leber hereditary optic neuropathy (LHON) in a population of 2,173,800 individuals in the North East of England. We identified 16 genealogically unrelated families who harbor one of the three primary mitochondrial DNA (mtDNA) mutations that cause LHON. Two of these families were found to be linked genetically to a common maternal founder. A de novo mtDNA mutation (G3460A) was identified in one family. The minimum point prevalence of visual failure due to LHON within this population was 3.22 per 100,000 (95% CI 2.47–3.97 per 100,000), and the minimum point prevalence for mtDNA LHON mutations was 11.82 per 100,000 (95% CI 10.38–13.27 per 100,000). These results indicate that LHON is not rare but has a population prevalence similar to autosomally inherited neurological disorders. The majority of individuals harbored only mutant mtDNA (homoplasmy), but heteroplasmy was detected in ∼12% of individuals. Overall, however, ∼33% of families with LHON had at least one heteroplasmic individual. The high incidence of heteroplasmy in pedigrees with LHON raises the possibility that a closely related maternal relative of an index case may not harbor the mtDNA mutation, highlighting the importance of molecular genetic testing for each maternal family member seeking advice about their risks of visual failure.
414 citations
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TL;DR: It is shown here that TERT, the catalytic subunit of human telomerase, protects human fibroblasts against oxidative stress and proposes protection of mitochondria under mild stress as a novel function of TERT.
Abstract: Telomerase is a ribonucleoprotein that counteracts telomere shortening and can immortalise human cells. There is also evidence for a telomere-independent survival function of telomerase. However, its mechanism is not understood. We show here that TERT, the catalytic subunit of human telomerase, protects human fibroblasts against oxidative stress. While TERT maintains telomere length under standard conditions, telomeres under increased stress shorten as fast as in cells without active telomerase. This is because TERT is reversibly excluded from the nucleus under stress in a dose- and time-dependent manner. Extranuclear telomerase colocalises with mitochondria. In TERT-overexpressing cells, mtDNA is protected, mitochondrial membrane potential is increased and mitochondrial superoxide production and cell peroxide levels are decreased, all indicating improved mitochondrial function and diminished retrograde response. We propose protection of mitochondria under mild stress as a novel function of TERT.
414 citations
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23 Apr 1974TL;DR: In this paper, a new method of expressing synchronization is presented and the motivations and considerations which led to this method are explained, and a means of automatically translating path expressions to existing primitive synchronization operations is given.
Abstract: A new method of expressing synchronization is presented and the motivations and considerations which led to this method are explained. Synchronization rules, given by ‘path expressions’, are incorporated into the type definitions which are used to introduce data objects shared by several asynchronous processes. It is shown that the method's ability to express synchronization rules is equivalent to that of P and V operations, and a means of automatically translating path expressions to existing primitive synchronization operations is given.
414 citations
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Goethe University Frankfurt1, Charité2, Kyung Hee University3, Lille University of Science and Technology4, University of Paris5, Charles University in Prague6, University of Western Brittany7, Inje University8, Erasmus University Rotterdam9, Harvard University10, University of Turku11, Newcastle University12, University of Hong Kong13, Comenius University in Bratislava14, University of Granada15, University of Nantes16, University of Rennes17, Pierre-and-Marie-Curie University18, French Institute of Health and Medical Research19, University of Milan20, University of Marburg21, Yonsei University22, Instituto Português de Oncologia Francisco Gentil23, Seoul National University24, Hannover Medical School25, University of Padua26, University of Zurich27, University of Hamburg28, University of New South Wales29, Sheba Medical Center30, Tel Aviv University31, University of Copenhagen32, Southmead Hospital33, University of Porto34, University of Catania35, University of Kiel36, University of Silesia in Katowice37, Medical University of Vienna38
TL;DR: Long-distance inverse-polymerase chain reaction was used to characterize the chromosomal rearrangement of individual acute leukemia patients and revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level.
Abstract: Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (∼90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.
414 citations
Authors
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Name | H-index | Papers | Citations |
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Martin White | 196 | 2038 | 232387 |
Barry Halliwell | 173 | 662 | 159518 |
Adrian L. Harris | 170 | 1084 | 120365 |
Jorge E. Cortes | 163 | 2784 | 124154 |
Frank J. Gonzalez | 160 | 1144 | 96971 |
David W. Bates | 159 | 1239 | 116698 |
Nicholas J. Talley | 158 | 1571 | 90197 |
Hans Lassmann | 155 | 724 | 79933 |
Stephen J. O'Brien | 153 | 1062 | 93025 |
Edmund T. Rolls | 153 | 612 | 77928 |
David J. Brooks | 152 | 1056 | 94335 |
Andrew J. Lees | 140 | 877 | 91605 |
Daniel Thomas | 134 | 846 | 84224 |
Peter Hall | 132 | 1640 | 85019 |
Paul Brennan | 132 | 1221 | 72748 |